Tolerogenic Iron Oxide Nanoparticles in Type 1 Diabetes: Biodistribution and Pharmacokinetics Studies in Nonobese Diabetic Mice

Abstract

Nanoparticle (NP) administration is among the most attractive approaches to exploit the synergy of different copackaged molecules for the same target. In this work, iron oxide NPs are surface-engineered for the copackaging of the autoantigen proinsulin, a major target of adaptive immunity in type 1 diabetes (T1D), and 2-(1'H-indole-3'-carbonyl)-thiazole-4-carboxylic acid methylester (ITE), a small drug conditioning a tolerogenic environment. Magnetic resonance imaging (MRI) combined with magnetic quantification are used to investigate NP biokinetics in nonobese diabetic (NOD) mice and control mice in different organs. Different NP biodistribution, with in particular enhanced kidney elimination and a stronger accumulation in the pancreas for prediabetic NOD mice, is observed. This is related to preferential NP accumulation in the pancreatic inflammatory zone and to enhancement of renal elimination by diabetic nephropathy. For both mouse strains, an MRI T2 contrast enhancement at 72 h in the liver, pancreas, and kidneys, and indicating recirculating NPs, is also found. This unexpected result is confirmed by magnetic quantification at different time points as well as by histological evaluation. Besides, such NPs are potential MRI contrast agents for early diagnosis of T1D.

Magnetic nanoparticles: A new diagnostic and treatment platform for rheumatoid arthritis

“…They were be found in specific organs or regions with monocytes accumulation, especially the aorta of atherosclerosis model mice, through in vivo imaging system (IVIS) imaging and MRI 101 . MNPs co‐packaging of the autoantigen proinsulin, gained preferential accumulation in the pancreatic inflammatory zone and enhanced kidney elimination, which were used as potential MRI contrast agents for early diagnosis of Type 1 diabetes 102 . MNPs wrapped with vesicles derived from MSCs achieved effective targeting therapies for spinal cord injury 103 .…”

Magnetic properties of hematite (α − Fe2O3) nanoparticles synthesized by sol-gel synthesis method: The influence of particle size and particle size distribution

“…As the size of the particles decreases, the magnetic properties of the iron(III) oxides exhibit peculiar properties, which differ from those of bulk counterpart materials, because of nanoscale confinement and surface effects. They have a range of practical applications in different technological areas, such as solar cell, pigment, microwave absorption, catalysis, environ-ment protection, gas sensor, magnetic storage, clinical diagnosis and treatment, etc [31][32][33][34][35][36][37][38][39][40].…”

Toxicity of microwave-assisted biosynthesized zinc nanoparticles in mice: a preliminary study

“…It has been reported that $85% of Zn is distributed in the bone and muscle, and about 11% in the skin and the liver, while the remaining is distributed in other tissues [38]. However, target organs for NPs can be different, since the liver and spleen are the main target organs for cerium oxide, and liver, pancreas, and kidney for iron oxide NPs [39,40]. The size of NPs may also affect its distribution in different tissues, as 20 and 120 nm ZnO were mostly retained in the bone, kidney, and pancreas [41].…”